Evidence for liver benefits with SGLT2 inhibition
medwireNews: Two small studies reported at the virtual ADA 80th Scientific Sessions have demonstrated positive effects of sodium-glucose cotransporter (SGLT)2 inhibitors on the liver.
The first, presented by Shigenori Hiruma (Toho University Graduate School of Medicine, Tokyo, Japan), found that people with type 2 diabetes and elevated liver enzymes had a significantly greater reduction in intrahepatic lipid content with empagliflozin 10 mg/day than sitagliptin 50 mg/day during 12 weeks of treatment, of approximately 20% versus no change.
The 44 study participants were aged around 50 years on average, with diabetes of 3–4 years’ duration, and all were overweight. They were randomly assigned to take one of the two study treatments, which the researchers had chosen because of previous reports that these medications could reduce pericardial fat. However, this did not occur with either in the current study.
People taking empagliflozin also had a significantly higher rate of glucose disappearance than those taking sitagliptin, indicating a larger improvement in muscle insulin sensitivity.
Expert commentary: Could SGLT2 inhibition protect the liver in type 2 diabetes?
The second study – reported by Hirokazu Takahashi (Saga University, Japan) – involved 55 patients with liver-proven non-alcoholic fatty liver disease and glycated hemoglobin levels greater than 6.0% (42 mmol/mol).
During 72 weeks of treatment, those randomly assigned to take ipragliflozin 50 mg/day had a significant reduction in levels of gamma-glutamyl transferase, compared with no change in patients assigned to enhanced lifestyle therapy plus medications other than SGLT2 inhibitors, pioglitazone, or glucagon-like peptide-1 receptor agonists.
Moreover, significantly more study participants taking ipragliflozin than controls had improvements in hepatocyte ballooning (52.4 vs 24.0%) and fibrosis (57.1 vs 16.0%).
Among study participants without non-alcoholic steatohepatitis (NASH) at baseline, none of those taking ipragliflozin progressed to NASH, compared with 33.3% of those in the control group. And among those who already had NASH at study entry, this resolved in 66.7% of those taking ipragliflozin versus 27.3% of the control group.
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